R516A is one of the new substitutes for R134a refrigerant in water-cooled chillers. The COP (coefficient of performance) and discharge temperatures of R516A and R134a are compared through a single-stage vapor compression cycle. Under nominal and variable operating conditions, the performances of a small water-cooled chiller charged with R134a and R516A are tested and compared. The cost changes of replacing R134a with R516A in the water-cooled chiller are discussed. The conclusions indicate that, in the theoretical cycle, the COP of R516A is 1.5% lower than that of R134a, and the discharge temperature is 4.9-6.0 ℃ lower than that of R134a. Under nominal operating conditions, there is a certain performance gap between the R516A chiller and the R134a chiller, with a COP difference of 4.9%-7.2%. Under variable operating conditions, the performance of the R516A chiller is basically equivalent to that of the R134a chiller, and the COP gap is reduced to 0.5%-2.3%. Owing to the mild flammability of R516A, the cost of the R516A chiller is 10%-15% higher than that of the R134a chiller.